85% of those with schizophrenia never recover. They also have an increased morbidity in physical diseases, especially immunological ones. In recent years, several studies have demonstrated a link between inflammation/autoimmunity and schizophrenia. Between 2019-2022, we have investigated in an open pilot study whether nine severely ill therapy-resistant patients with schizophrenia spectrum disorder improve with the anti-inflammatory drug rituximab. Rituximab is a well-proven drug (anti-CD20 antibodies) commonly used in MS and rheumatoid arthritis. Treatment is given every six months. Rituximab has not previously been tested in mental illness so our pilot study is groundbreaking. We have seen very good results in several patients with SSD (6/9), so we intend to proceed with a placebo-controlled study in 104 patients (18-51 years). Rituximab is given as a single drop. Serious side effects can occur, but are extremely rare. The study patients continue with their regular drug treatment which reduces the risk of deterioration. We will evaluate the effect after 12 weeks using established evaluation instruments and examine general improvement, function and self-rated health. Patients will be followed for 6 months. Side effects and signs of inflammation will be investigated. If the treatment proves effective, it will most likely revolutionize the understanding and treatment recommendations for a severely affected patient group.